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Exposure to Disinfection By-products, Fetal Growth, and Prematurity: A Systematic Review and Meta-analysis

Grellier, Jamesa; Bennett, Jamesa; Patelarou, Evridikib; Smith, Rachel B.a; Toledano, Mireille B.a; Rushton, Lesleya; Briggs, David J.a; Nieuwenhuijsen, Mark J.a,c

doi: 10.1097/EDE.0b013e3181d61ffd
Perinatal: Review Article

Background: Exposure to total trihalomethanes in drinking water has been associated with several adverse birth outcomes relating to fetal growth and prematurity.

Methods: We carried out a systematic review and meta-analysis of epidemiologic studies featuring original peer-reviewed data on the association of total trihalomethane exposure and health outcomes related to fetal growth and prematurity.

Results: A comprehensive literature search yielded 37 studies, 15 of which were selected for the extraction of relative risks relating adverse birth outcomes to trihalomethane exposure. Sufficient data were available for meta-analyses to be carried out for 4 adverse birth outcomes: low birth weight (LBW), term low birth weight (term LBW), preterm delivery, and small for gestational age (SGA) (including intra uterine growth retardation). We found little or no evidence for associations between third trimester trihalomethane exposure and LBW (odds ratio per 10 μg total trihalomethane/L = 1.00 [95% confidence interval = 0.97–1.03]), term LBW (1.03 [0.93–1.15]), or preterm delivery (0.99 [0.98–1.00]), but some evidence for SGA (1.01 [1.00–1.02]).

Conclusions: There was little or no evidence for associations between total trihalomethane concentration and adverse birth outcomes relating to fetal growth and prematurity, with the possible exception of SGA. We discuss these findings and the uncertainties—relating particularly to exposure—that may have affected them.


From the aDepartment of Epidemiology and Public Health, Imperial College London, London, United Kingdom; bDepartment of Social Medicine, University of Crete, Heraklion, Greece; and cCenter for Research in Environmental Epidemiology (CREAL), IMIM, CIBERESP, Barcelona, Spain.

Submitted 24 March 2009; accepted 2 October 2009.

Supported by the Integrated Assessment of Health Risks of Environmental Stressors in Europe (INTARESE) project, which is funded under the European Commission under the Sixth Framework Programme (2002–2006) grant GOCE-CT-2005–018385.

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Correspondence: James Grellier, Department of Epidemiology and Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. E-mail:

© 2010 Lippincott Williams & Wilkins, Inc.